A. Bruni, et al., report that the brain glucose level in mice injected via the caudal vein with phosphatidylserine extracted from bovine brain is increased by about 4 fold the level in the control group (A. Bruni et al., Nature, Vol. 260, pp. 331, 1976).
A. Zanotti et al., also report that the oral administration of phosphatidylserine extracted from bovine brain to aged rats with memory deficits for 12 weeks improved the performance of the aged rats (A. Zanotti et al., Psychopharmacology Berl., Vol. 99, pp. 316, 1989).
Furthermore it is confirmed at a double-blind placebo-controlled clinical trial for humans the efficacy of phosphatidylserine extracted from bovine brain in improving the memory impairment in Alzheimer's disease and during the aging stage (P. J. Delwaide et al., Acta Neurol. Scand., Vol. 73, pp. 136, 1986; R. R. Engel et al., Eur. Neuropsychopharmacol., Vol. 2, pp. 149, 1992; T. Cenacci et al., Aging Clin. Exp. Res., Vol. 5, pp. 123, 1993).
As has been described above, bovine brain-derived phosphatidylserine having the effect of increasing brain glucose level has an effect of improving the cerebration in rats and humans. Therefore, it is indicated that the degree of the increase in brain glucose level is an important indicator for selecting a substance with the action of improving cerebration.
However, it is believed that in general unsaturated fatty acid is bound to the beta position of phospholipid, and in natural phosphatidylserine, such as that derived from animal brain, more than ninety-two (92) percent of the fatty acid at beta position contains oleic acid (B. F. Szuhaj & G. R. List, "Lecithins", Am. Oil Chem. Soc., U.S.A., pp. 145, 1985).
In phosphatidylserines produced through a transphosphatidylation reaction with phospholipase-D (PLD), a known method of industrially producing phospholipids, most of fatty acid at beta position thereof was the same as that of the starting material, for example, linoleic acid and linolenic acid when using soybean lecithin, or oleic acid and linoleic acid when using yolk lecithin.
Recently, there have been conducted a variety of studies on n-3 and n-6 groups of long chain unsaturated fatty acids, and there have been conducted many laboratory animal experimentations on the physiologic activities of n-3 group long chain unsaturated fatty acids, including the improvement of learning performance. From these background, it may be possible that, if material combining above noted long chain unsaturated fatty acid and phosphatidylserine, such as phosphatidylserine comprising long chain unsaturated fatty acid in its molecule was produced, summation or synergistic effect of both phosphatidylserine and long chain unsaturated fatty acid will be effective and better cerebration improver may be obtained.
However, there is not known among currently available phosphatidylserine one which may be industrially produced with lower cost and comprises a long chain unsaturated fatty acid of n-3 or n-6 (except linoleic acid) group at beta position.
For example, it has been proposed that a phosphatidylserine derivative having a specific fatty acid at beta position of glycerol structure, which may activate proteinkinase-C (PKC) is a material which is a composition of long chain unsaturated fatty acid and phosphatidylserine for the estimation of the summation or synergistic effect as stated above (Japanese Patent-Laid Open No. 6-279311). In this Japanese patent, it is described that the experiment has been conducted in the condition that the phosphatidylserine derived from bovine brain which is effective for the clinical improvement of cerebration is a type of composition of a variety of fatty acids and the efficacy is not yet confirmed when structural fatty acid is specified, and also described that from the experiment conducted as such, specific proteinkinase-C activity has been confirmed if saturated fatty acid (14 to 18 carbon atoms) is at the alpha position and linoleic acid, linolenic acid, arachidonic acid, docosahexaenoic acid (DHA) are at the beta position.
For producing phosphatidylserine having such specific structure, a method is disclosed in the above identified Japanese patent that diacyl phospholipids are transformed to liso phospholipids with phospholipase A.sub.2, then the specific phospholipid obtained by combining fatty acid in chemical synthesis arc transformed to phosphatidylserine through transphosphatidylation with phospholipase-D. This method is associated with complex multistage reaction and chemical synthesis so that the phosphatidylserine is not suitable for food stuff and that production cost is higher.
Also reported is that glycerol derivative having specific structure at alpha- and beta position fatty acids has the efficacy of improving learning performance (Japanese Patent Laid-Open No. 6-256179). However, this Japanese patent teaches that the primary structure for improvement is rather structural alpha- and beta fatty acids of the glycerol derivative, and the residue at gamma position, or glycerol-3-phosphoryl-X (X means hydroxyl, choline, or ethanolamine group) is not directly concerning to the improvement of the learning performance. Therefore, this glycerol derivative is different from the phosphatidylserine with summation or synergistic effect estimated as stated above in the combination of fatty acids having improvement effect of learning performance.
The producing method of glycerol derivative disclosed in the above noted second Japanese patent is of either separation from natural compound or of chemical synthesis or process with phospholipase-C, and this may not be a preferable method of industrial production for food.